Technical Field of the Invention
The present invention relates to pharmaceutical compositions based on a compound of the avermectin family comprising at least one fatty phase and at least one aqueous phase, said compound of the avermectin family being solubilized in said fatty phase.
The present invention relates more particularly to ivermectin-based pharmaceutical compositions comprising at least one fatty phase and at least one aqueous phase, the ivermectin being solubilized in said fatty phase.
This invention also relates to the formulation thereof and to the administration of such pharmaceutical compositions for the treatment of dermatological conditions, in particular rosacea.
Description of Background and/or Related and/or Prior Art
Ivermectin is a mixture of two compounds belonging to the class of avermectins, 5-O-demethyl-22,23-dihydroavermectin A1a and 5-O-demethyl-22,23-dihydroavermectin A1b. They are also known under the trademarks 22,23-dihydroavermectin B1a and 22,23-dihydroavermectin B1b. Ivermectin contains at least 80% of 22,23-dihydroavermectin B1a and less than 20% of 22,23-dihydroavermectin B1b. This active agent forms part of the class of avermectins, a group of macrocyclic lactones produced by the bacterium Streptomyces avermitilis (Reynolds JEF (Ed) (1993) Martindale, The extra pharmacopoeia. 29th Edition. Pharmaceutical Press, London). Avermectins include in particular ivermectin, invermectin, avermectin, abamectin, doramectin, eprinomectin and selamectin.
Ivermectin is more particularly an anthelmintic. It has been administered in humans in the treatment of onchocerciasis caused by onchocerca volvulus, of gastrointestinal strongyloidiasis (anguillulosis) (product Stomectol®) and of human scabies (Meinking T L et al., N. Engl. J. Med., 1995 Jul. 6; 333(1): 26-30 The treatment of scabies with ivermectin) and also in the treatment of microfilaremia diagnosed or suspected in individuals suffering from lymphatic filariosis due to Wuchereria bancrofti.
Dermatological conditions are often associated with increased sensitivity of the skin, particularly in the case of rosacea, which is an inflammatory dermatosis that affects mainly the central part of the face and is characterized, inter alia, by reddening of the face, hot flashes and facial erythemia. This type of pathology requires in particular the application of pharmaceutical formulations that are easy to spread and give the user a pleasant feeling of well-being.
Need therefore exists for topical pharmaceutical compositions containing at least one compound of the avermectin family, and more particularly ivermectin, which is completely suited to the pathological condition and specifically to sensitive skin, which is industrially acceptable, i.e., the formulation of which is physically stable (without phase separation) and chemically stable (without modification of the stability of the active agent) and which optimizes the penetration of ivermectin into the skin.
Ivermectin is a compound that is chemically unstable on contact with water. In order to stabilize it, various solutions have been provided in the prior art: EP 0,045,655 proposes forming micelles of surfactants which surround the ivermectin in order to protect it against water; other applications, such as WO 01/60380 or WO 97/26895, propose using aqueous solvents for active agents, such as N-methyl-2-pyrrolidone. Finally, WO 2004/093886 and WO 2005/089806 describe emulsions comprising an oily phase and an aqueous phase, said aqueous phase comprising a micellar active phase containing ivermectin. Unfortunately, these concepts do not allow optimum stability of the ivermectin.